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Imaging of MELAS

  • Imaging (L Mechtler, Section Editor)
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Abstract

Mitochondrial diseases are multisystem disorders that frequently involve the central nervous system. The clinical presentation of these disorders may be challenging to differentiate from cerebrovascular disorders. Various imaging techniques are now available that provide a wide range of imaging modalities during initial clinical evaluation and throughout the disease course. Recent technological advancements have introduced advanced neuroimaging modalities that provide detailed information of metabolic disorders at the tissue level. Imaging findings, though diverse, usually have characteristic features that support differentiating these disorders from vascular syndromes. This article provides an overview of various neuroimaging modalities available along with the advent of new imaging techniques being utilized in these disorders.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Pavlakis SG, Phillips PC, DiMauro S, De Vivo DC, Rowland LP. Mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes: a distinctive clinical syndrome. Ann Neurol. 1984;16(4):481–8. doi:10.1002/ana.410160409.

    Article  CAS  PubMed  Google Scholar 

  2. DiMauro S, Schon EA. Mitochondrial disorders in the nervous system. Annu Rev Neurosci. 2008;31:91–123. doi:10.1146/annurev.neuro.30.051606.094302.

    Article  CAS  PubMed  Google Scholar 

  3. DiMauro S, Schon EA. Mitochondrial respiratory-chain diseases. N Engl J Med. 2003;348(26):2656–68. doi:10.1056/NEJMra022567.

    Article  CAS  PubMed  Google Scholar 

  4. Iizuka T, Sakai F. Pathogenesis of stroke-like episodes in MELAS: analysis of neurovascular cellular mechanisms. Curr Neurovasc Res. 2005;2(1):29–45.

    Article  CAS  PubMed  Google Scholar 

  5. Malhotra K, Liebeskind DS. Imaging in Endovascular Stroke Trials. J Neuroimaging. 2015;25(4):517–27. doi:10.1111/jon.12272.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Goto Y, Horai S, Matsuoka T, Koga Y, Nihei K, Kobayashi M, et al. Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS): a correlative study of the clinical features and mitochondrial DNA mutation. Neurology. 1992;42(3 Pt 1):545–50.

    Article  CAS  PubMed  Google Scholar 

  7. Yoshida T, Ouchi A, Miura D, Shimoji K, Kinjo K, Sueyoshi T, et al. MELAS and reversible vasoconstriction of the major cerebral arteries. Int Med (Tokyo, Japan). 2013;52(12):1389–92.

    Article  Google Scholar 

  8. Yeh HL, Chen YK, Chen WH, Wang HC, Chiu HC, Lien LM, et al. Perfusion status of the stroke-like lesion at the hyperacute stage in MELAS. Brain Dev. 2013;35(2):158–64. doi:10.1016/j.braindev.2012.03.017.

    Article  PubMed  Google Scholar 

  9. Ito H, Mori K, Kagami S. Neuroimaging of stroke-like episodes in MELAS. Brain Dev. 2011;33(4):283–8. doi:10.1016/j.braindev.2010.06.010.

    Article  PubMed  Google Scholar 

  10. Haas R, Dietrich R. Neuroimaging of mitochondrial disorders. Mitochondrion. 2004;4(5–6):471–90. doi:10.1016/j.mito.2004.07.008.

    Article  CAS  PubMed  Google Scholar 

  11. Ito H, Mori K, Harada M, Minato M, Naito E, Takeuchi M, et al. Serial brain imaging analysis of stroke-like episodes in MELAS. Brain Dev. 2008;30(7):483–8. doi:10.1016/j.braindev.2008.01.003.

    Article  PubMed  Google Scholar 

  12. Allard JC, Tilak S, Carter AP. CT and MR of MELAS syndrome. AJNR Am J Neuroradiol. 1988;9(6):1234–8.

    CAS  PubMed  Google Scholar 

  13. Johnson EC, West TW, Ko NU, Strober JB. A 41-year-old man with new headache and altered mental status. Neurohospitalist. 2011;1(1):48–54. doi:10.1177/1941875210385948.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Lazzaro MA, Malhotra K, Mohammad YM. The role of antithrombotics in secondary stroke prevention. Semin Neurol. 2010;30(5):492–500. doi:10.1055/s-0030-1268860.

    Article  PubMed  Google Scholar 

  15. Finsterer J, Barton P. Regression of stroke-like lesions in MELAS-syndrome after seizure control. Epileptic Disord. 2010;12(4):330–4. doi:10.1684/epd.2010.0338.

    PubMed  Google Scholar 

  16. Carolei A, Sacco S. Headache attributed to arteritis, cerebral venous thrombosis, and other vascular intracranial disturbances. Handb Clin Neurol. 2010;97:529–40. doi:10.1016/s0072-9752(10)97048-6.

    Article  PubMed  Google Scholar 

  17. Jamieson DG, Cheng NT, Skliut M. Headache and acute stroke. Curr Pain Headache Rep. 2014;18(9):444. doi:10.1007/s11916-014-0444-1.

    Article  Google Scholar 

  18. Wang YX, Le WD. Progress in Diagnosing Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like Episodes. Chin Med J (Engl). 2015;128(13):1820–5. doi:10.4103/0366-6999.159360.

    Article  Google Scholar 

  19. Kim IO, Kim JH, Kim WS, Hwang YS, Yeon KM, Han MC. Mitochondrial myopathy-encephalopathy-lactic acidosis-and strokelike episodes (MELAS) syndrome: CT and MR findings in seven children. AJR Am J Roentgenol. 1996;166(3):641–5. doi:10.2214/ajr.166.3.8623642.

    Article  CAS  PubMed  Google Scholar 

  20. Chung SH, Chen SC, Chen WJ, Lee CC. Symmetric basal ganglia calcification in a 9-year-old child with MELAS. Neurology. 2005;65(9), E19. doi:10.1212/01.wnl.0000184112.34211.d1.

    Article  PubMed  Google Scholar 

  21. Hirano M, Pavlakis SG. Mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS): current concepts. J Child Neurol. 1994;9(1):4–13.

    Article  CAS  PubMed  Google Scholar 

  22. Davis PC, Hoffman Jr JC, Braun IF, Ahmann P, Krawiecki N. MR of Leigh’s disease (subacute necrotizing encephalomyelopathy). AJNR Am J Neuroradiol. 1987;8(1):71–5.

    CAS  PubMed  Google Scholar 

  23. Goodfellow JA, Dani K, Stewart W, Santosh C, McLean J, Mulhern S, et al. Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes: an important cause of stroke in young people. Postgrad Med J. 2012;88(1040):326–34. doi:10.1136/postgradmedj-2011-130326.

    Article  CAS  PubMed  Google Scholar 

  24. Gire C, Girard N, Nicaise C, Einaudi MA, Montfort MF, Dejode JM. Clinical features and neuroradiological findings of mitochondrial pathology in six neonates. Childs Nerv Syst. 2002;18(11):621–8. doi:10.1007/s00381-002-0621-0.

    Article  CAS  PubMed  Google Scholar 

  25. Moroni I, Bugiani M, Bizzi A, Castelli G, Lamantea E, Uziel G. Cerebral white matter involvement in children with mitochondrial encephalopathies. Neuropediatrics. 2002;33(2):79–85. doi:10.1055/s-2002-32372.

    Article  CAS  PubMed  Google Scholar 

  26. Pauli W, Zarzycki A, Krzysztalowski A, Walecka A. CT and MRI imaging of the brain in MELAS syndrome. Pol J Radiol. 2013;78(3):61–5. doi:10.12659/pjr.884010.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Wang XY, Noguchi K, Takashima S, Hayashi N, Ogawa S, Seto H. Serial diffusion-weighted imaging in a patient with MELAS and presumed cytotoxic oedema. Neuroradiology. 2003;45(9):640–3. doi:10.1007/s00234-003-1029-6.

    Article  CAS  PubMed  Google Scholar 

  28. Yoneda M, Maeda M, Kimura H, Fujii A, Katayama K, Kuriyama M. Vasogenic edema on MELAS: a serial study with diffusion-weighted MR imaging. Neurology. 1999;53(9):2182–4.

    Article  CAS  PubMed  Google Scholar 

  29. Jian-Ren L. Precipitation of stroke-like event by chickenpox in a child with MELAS syndrome. Neurol India. 2005;53(3):323–5.

    Article  PubMed  Google Scholar 

  30. Yonemura K, Hasegawa Y, Kimura K, Minematsu K, Yamaguchi T. Diffusion-weighted MR imaging in a case of mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes. AJNR Am J Neuroradiol. 2001;22(2):269–72.

    CAS  PubMed  Google Scholar 

  31. Tzoulis C, Bindoff LA. Serial diffusion imaging in a case of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes. Stroke. 2009;40(2):e15–7. doi:10.1161/strokeaha.108.523118.

    Article  PubMed  Google Scholar 

  32. Kim JH, Lim MK, Jeon TY, Rha JH, Eo H, Yoo SY, et al. Diffusion and perfusion characteristics of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episode) in thirteen patients. Korean J Radiol. 2011;12(1):15–24. doi:10.3348/kjr.2011.12.1.15.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Chinnery PF. Mitochondrial Disorders Overview. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, editors. GeneReviews(R). Seattle (WA): University of Washington, Seattle; 1993. All rights reserved.

    Google Scholar 

  34. Dindyal S, Mistry K, Angamuthu N, Smith G, Hilton D, Arumugam P, et al. MELAS syndrome presenting as an acute surgical abdomen. Ann R Coll Surg Engl. 2014;96(1):101e–3e. doi:10.1308/003588414x13824511649733.

    Article  CAS  PubMed  Google Scholar 

  35. Saneto RP, Friedman SD, Shaw DW. Neuroimaging of mitochondrial disease. Mitochondrion. 2008;8(5–6):396–413. doi:10.1016/j.mito.2008.05.003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Wilichowski E, Pouwels PJ, Frahm J, Hanefeld F. Quantitative proton magnetic resonance spectroscopy of cerebral metabolic disturbances in patients with MELAS. Neuropediatrics. 1999;30(5):256–63. doi:10.1055/s-2007-973500.

    Article  CAS  PubMed  Google Scholar 

  37. Moller HE, Kurlemann G, Putzler M, Wiedermann D, Hilbich T, Fiedler B. Magnetic resonance spectroscopy in patients with MELAS. J Neurol Sci. 2005;229–230:131–9. doi:10.1016/j.jns.2004.11.014.

    Article  PubMed  Google Scholar 

  38. Osborn AG, Salzman KL, Jhaveri MD, Barkovich AJ. Diagnostic imaging: brain. Elsevier Health Sciences; 2015

  39. Abe K, Yoshimura H, Tanaka H, Fujita N, Hikita T, Sakoda S. Comparison of conventional and diffusion-weighted MRI and proton MR spectroscopy in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like events. Neuroradiology. 2004;46(2):113–7. doi:10.1007/s00234-003-1138-2.

    Article  CAS  PubMed  Google Scholar 

  40. Kaufmann P, Engelstad K, Wei Y, Kulikova R, Oskoui M, Sproule DM, et al. Natural history of MELAS associated with mitochondrial DNA m.3243A>G genotype. Neurology. 2011;77(22):1965–71. doi:10.1212/WNL.0b013e31823a0c7f.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Weiduschat N, Kaufmann P, Mao X, Engelstad KM, Hinton V, DiMauro S, et al. Cerebral metabolic abnormalities in A3243G mitochondrial DNA mutation carriers. Neurology. 2014;82(9):798–805. doi:10.1212/wnl.0000000000000169.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Virtanen SM, Lindroos MM, Majamaa K, Nuutila P, Borra RJ, Parkkola R. Voxelwise analysis of diffusion tensor imaging and structural MR imaging in patients with the m.3243A>G mutation in mitochondrial DNA. AJNR Am J Neuroradiol. 2011;32(3):522–6. doi:10.3174/ajnr.A2309.

    Article  CAS  PubMed  Google Scholar 

  43. Noguchi A, Shoji Y, Matsumori M, Komatsu K, Takada G. Stroke-like episode involving a cerebral artery in a patient with MELAS. Pediatr Neurol. 2005;33(1):70–1. doi:10.1016/j.pediatrneurol.2005.01.013.

    Article  PubMed  Google Scholar 

  44. Iizuka T, Goto Y, Miyakawa S, Sato M, Wang Z, Suzuki K, et al. Progressive carotid artery stenosis with a novel tRNA phenylalanine mitochondrial DNA mutation. J Neurol Sci. 2009;278(1–2):35–40. doi:10.1016/j.jns.2008.11.016.

    Article  CAS  PubMed  Google Scholar 

  45. Ooiwa Y, Uematsu Y, Terada T, Nakai K, Itakura T, Komai N, et al. Cerebral blood flow in mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes. Stroke. 1993;24(2):304–9.

    Article  CAS  PubMed  Google Scholar 

  46. Molnar MJ, Valikovics A, Molnar S, Tron L, Dioszeghy P, Mechler F, et al. Cerebral blood flow and glucose metabolism in mitochondrial disorders. Neurology. 2000;55(4):544–8.

    Article  CAS  PubMed  Google Scholar 

  47. Ikawa M, Okazawa H, Arakawa K, Kudo T, Kimura H, Fujibayashi Y, et al. PET imaging of redox and energy states in stroke-like episodes of MELAS. Mitochondrion. 2009;9(2):144–8. doi:10.1016/j.mito.2009.01.011.

    Article  CAS  PubMed  Google Scholar 

  48. Nishioka J, Akita Y, Yatsuga S, Katayama K, Matsuishi T, Ishibashi M, et al. Inappropriate intracranial hemodynamics in the natural course of MELAS. Brain Dev. 2008;30(2):100–5. doi:10.1016/j.braindev.2007.06.008.

    Article  PubMed  Google Scholar 

  49. Thajeb P, Wu MC, Shih BF, Tzen CY, Chiang MF, Yuan RY. Brain single photon emission computed tomography in patients with A3243G mutation in mitochondrial DNA tRNA. Ann N Y Acad Sci. 2005;1042:48–54. doi:10.1196/annals.1338.005.

    Article  CAS  PubMed  Google Scholar 

  50. Koga Y, Akita Y, Junko N, Yatsuga S, Povalko N, Fukiyama R, et al. Endothelial dysfunction in MELAS improved by l-arginine supplementation. Neurology. 2006;66(11):1766–9. doi:10.1212/01.wnl.0000220197.36849.1e.

    Article  CAS  PubMed  Google Scholar 

  51. Koga Y, Povalko N, Nishioka J, Katayama K, Kakimoto N, Matsuishi T. MELAS and L-arginine therapy: pathophysiology of stroke-like episodes. Ann N Y Acad Sci. 2010;1201:104–10. doi:10.1111/j.1749-6632.2010.05624.x.

    Article  CAS  PubMed  Google Scholar 

  52. Iizuka T, Sakai F, Kan S, Suzuki N. Slowly progressive spread of the stroke-like lesions in MELAS. Neurology. 2003;61(9):1238–44.

    Article  PubMed  Google Scholar 

  53. Tsujikawa T, Yoneda M, Shimizu Y, Uematsu H, Toyooka M, Ikawa M, et al. Pathophysiologic evaluation of MELAS strokes by serially quantified MRS and CASL perfusion images. Brain Dev. 2010;32(2):143–9. doi:10.1016/j.braindev.2008.12.003.

    Article  PubMed  Google Scholar 

  54. Ikawa M, Yoneda M, Muramatsu T, Matsunaga A, Tsujikawa T, Yamamoto T, et al. Detection of preclinically latent hyperperfusion due to stroke-like episodes by arterial spin-labeling perfusion MRI in MELAS patients. Mitochondrion. 2013;13(6):676–80. doi:10.1016/j.mito.2013.09.007.

    Article  CAS  PubMed  Google Scholar 

  55. Huppi PS, Inder TE. Magnetic resonance techniques in the evaluation of the perinatal brain: recent advances and future directions. Semin Neonatol. 2001;6(2):195–210. doi:10.1053/siny.2001.0039.

    Article  CAS  PubMed  Google Scholar 

  56. Majoie CB, Akkerman EM, Blank C, Barth PG, Poll-The BT, den Heeten GJ. Mitochondrial encephalomyopathy: comparison of conventional MR imaging with diffusion-weighted and diffusion tensor imaging: case report. AJNR Am J Neuroradiol. 2002;23(5):813–6.

    PubMed  Google Scholar 

  57. Xie S. MR OEF, imaging in MELAS. Methods Enzymol. 2014;547:433–44. doi:10.1016/b978-0-12-801415-8.00021-7.

    Article  CAS  PubMed  Google Scholar 

  58. De Volder A, Ghilain S, de Barsy T, Goffinet AM. Brain metabolism in mitochondrial encephalomyopathy: a PET study. J Comput Assist Tomogr. 1988;12(5):854–7.

    Article  PubMed  Google Scholar 

  59. Yu L, Xie S, Xiao J, Wang Z, Zhang X. Quantitative measurement of cerebral oxygen extraction fraction using MRI in patients with MELAS. PLoS One. 2013;8(11):e79859. doi:10.1371/journal.pone.0079859.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Malhotra K, Conners JJ, Lee VH, Prabhakaran S. Relative changes in transcranial Doppler velocities are inferior to absolute thresholds in prediction of symptomatic vasospasm after subarachnoid hemorrhage. J Stroke Cerebrovasc Dis. 2014;23(1):31–6. doi:10.1016/j.jstrokecerebrovasdis.2012.08.004.

    Article  PubMed  Google Scholar 

  61. Kodaka R, Itagaki Y, Matsumoto M, Nagai T, Okada S. A transcranial doppler ultrasonography study of cerebrovascular CO2 reactivity in mitochondrial encephalomyopathy. Stroke. 1996;27(8):1350–3.

    Article  CAS  PubMed  Google Scholar 

  62. Ganslandt O, Steinmeier R, Kober H, Vieth J, Kassubek J, Romstock J, et al. Magnetic source imaging combined with image-guided frameless stereotaxy: a new method in surgery around the motor strip. Neurosurgery. 1997;41(3):621–7. discussion 7–8.

    CAS  Google Scholar 

  63. Rossini PM, Tecchio F, Pizzella V, Lupoi D, Cassetta E, Pasqualetti P, et al. On the reorganization of sensory hand areas after mono-hemispheric lesion: a functional (MEG)/anatomical (MRI) integrative study. Brain Res. 1998;782(1–2):153–66.

    Article  CAS  PubMed  Google Scholar 

  64. Kamada K, Takeuchi F, Houkin K, Kitagawa M, Kuriki S, Ogata A, et al. Reversible brain dysfunction in MELAS: MEG, and (1)H MRS analysis. J Neurol Neurosurg Psychiatry. 2001;70(5):675–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Tschampa HJ, Urbach H, Greschus S, Kunz WS, Kornblum C. Neuroimaging characteristics in mitochondrial encephalopathies associated with the m.3243A>G MTTL1 mutation. J Neurol. 2013;260(4):1071–80. doi:10.1007/s00415-012-6763-4.

    Article  CAS  PubMed  Google Scholar 

  66. Lax NZ, Pienaar IS, Reeve AK, Hepplewhite PD, Jaros E, Taylor RW, et al. Microangiopathy in the cerebellum of patients with mitochondrial DNA disease. Brain. 2012;135(Pt 6):1736–50. doi:10.1093/brain/aws110.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Renard D, Taieb G. Neurological picture. Cortical susceptibility-weighted imaging hypointensity after stroke-like episode in MELAS. J Neurol Neurosurg Psychiatry. 2014;85(9):1055–6. doi:10.1136/jnnp-2013-306933.

    Article  PubMed  Google Scholar 

  68. Betts J, Jaros E, Perry RH, Schaefer AM, Taylor RW, Abdel-All Z, et al. Molecular neuropathology of MELAS: level of heteroplasmy in individual neurones and evidence of extensive vascular involvement. Neuropathol Appl Neurobiol. 2006;32(4):359–73. doi:10.1111/j.1365-2990.2006.00731.x.

    Article  CAS  PubMed  Google Scholar 

  69. Ramanathan RS, Malhotra K, Scott T. Teaching NeuroImages: diffuse cerebral neurosarcoidosis mimicking gliomatosis cerebri. Neurology. 2013;81(7):e46. doi:10.1212/WNL.0b013e3182a08d47.

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Authors and Affiliations

  1. Department of Neurology, Vascular Neurology Fellow, UCLA, Los Angeles, CA, USA

    Konark Malhotra

  2. Neurovascular Imaging Research Core, Neuroscience Research Building, 635 Charles E Young Drive South, Suite 225, Los Angeles, CA, 90095-7334, USA

    David S. Liebeskind

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Correspondence to David S. Liebeskind.

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Konark Malhotra declares no conflict of interest.

David S. Liebeskind declares NIH-NINDS grant support and being a consultant for Imaging Core Lab for Stryker and Medtronic.

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Malhotra, K., Liebeskind, D.S. Imaging of MELAS. Curr Pain Headache Rep 20, 54 (2016). https://doi.org/10.1007/s11916-016-0583-7

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